Verbale Definitheit und der vedische Injunktiv

Der Artikel knüpft an Karl Hoffmanns Ergebnisse zur Funktionsbestimmung des vedischen Injunktivs an und versucht anhand ausgewählter Stellen des Rigveda zu zeigen, dass der Injunktiv nicht nur ,bekannte‘ Sachverhalte bezeichnet, sondern überhaupt die ,definite‘ Weise ist, auf Sachverhalte bezugzunehmen. Mit dieser speziellen Funktion deckt der Injunktiv eine Teilmenge der Funktionen des Indikativs ab. Da der Injunktiv morphologisch aber einfacher ist als der Indikativ, sind vorhistorische Funktionsverschiebungen anzunehmen

A residual based a posteriori error estimator for an augmented mixed finite element method in linear elasticity

In this paper we develop a residual based a posteriori error analysis for an augmented mixed finite element method applied to the problem of linear elasticity in the plane. More precisely, we derive a reliable and efficient a posteriori error estimator for the case of pure Dirichlet boundary conditions. In addition, several numerical experiments confirming the theoretical properties of the estimator, and illustrating the capability of the corresponding adaptive algorithm to localize the singularities and the large stress regions of the solution, are also reporte

Asymptotic Behavior of the Einstein-Yang-Mills-Dilaton System for a Closed Friedmann-Lemaitre Universe

We study the coupled Einstein-Yang-Mills-Dilaton (EYMD) equations for a Fried\-mann-Le\-mai\-tre universe with constant curvature $k=1$. Our detailed analysis is restricted to the case where the dilaton potential and the cosmological constant vanish. Also assuming a static gauge field, we present analytical and numerical results on the behavior of solutions of the EYMD equations. For different values of the dilaton coupling constant we analyze the phase portrait for the time evolution of the dilaton field and give the behavior of the scale factor. It turns out that there are no inflationary stages in this model.Comment: 18 pages, Uuencoded gzip compressed tar file containing a latex file and 12 figures. The epsfig.sty is neede

Deciding logics of linear Kripke frames with scattered end pieces

We show that logics based on linear Kripke frames – with or without constant domains – that have a scattered end piece are not recursively enumerable.This is done by reduction to validity in all finite classical models

Neutrophil gelatinase-associated lipocalin (NGAL) predicts response to neoadjuvant chemotherapy and clinical outcome in primary human breast cancer

In our previous work we showed that NGAL, a protein involved in the regulation of proliferation and differentiation, is overexpressed in human breast cancer (BC) and predicts poor prognosis. In neoadjuvant chemotherapy (NACT) pathological complete response (pCR) is a predictor for outcome. The aim of this study was to evaluate NGAL as a predictor of response to NACT and to validate NGAL as a prognostic factor for clinical outcome in patients with primary BC. Immunohistochemistry was performed on tissue microarrays from 652 core biopsies from BC patients, who underwent NACT in the GeparTrio trial. NGAL expression and intensity was evaluated separately. NGAL was detected in 42.2% of the breast carcinomas in the cytoplasm. NGAL expression correlated with negative hormone receptor (HR) status, but not with other baseline parameters. NGAL expression did not correlate with pCR in the full population, however, NGAL expression and staining intensity were significantly associated with higher pCR rates in patients with positive HR status. In addition, strong NGAL expression correlated with higher pCR rates in node negative patients, patients with histological grade 1 or 2 tumors and a tumor size <40 mm. In univariate survival analysis, positive NGAL expression and strong staining intensity correlated with decreased disease-free survival (DFS) in the entire cohort and different subgroups, including HR positive patients. Similar correlations were found for intense staining and decreased overall survival (OS). In multivariate analysis, NGAL expression remained an independent prognostic factor for DFS. The results show that in low-risk subgroups, NGAL was found to be a predictive marker for pCR after NACT. Furthermore, NGAL could be validated as an independent prognostic factor for decreased DFS in primary human BC

Cannabinoid receptor CB2 drives HER2 pro-oncogenic signaling in breast cancer

Pharmacological activation of cannabinoid receptors elicits antitumoral responses in different models of cancer. However, the biological role of these receptors in tumor physio-pathology is still unknown. We analyzed CB2 cannabinoid receptor protein expression in two series of 166 and 483 breast tumor samples operated in the University Hospitals of Kiel, Tübingen and Freiburg between 1997 and 2010. CB2 mRNA expression was also analyzed in previously published DNA microarray datasets. The role of CB2 in oncogenesis was studied by generating a mouse line that expresses the HER2 rat ortholog (neu) and lacks CB2, and by a variety of biochemical and cell biology approaches in human breast cancer cells in culture and in vivo, upon modulation of CB2 expression by si/shRNAs and overexpression plasmids. CB2-HER2 molecular interaction was studied by co-localization, coimmunoprecipitation and proximity ligation assays. We show an association between elevated CB2 expression in HER2+ breast tumors and poor patient prognosis. We also demonstrate that genetic inactivation of CB2 impairs tumor generation and progression in MMTV-neu mice. Moreover, we show that HER2 upregulates CB2 expression by activating the transcription factor ELK1 via the ERK cascade, and that an increased CB2 expression activates the HER2 prooncogenic signaling machinery at the level of the tyrosine kinase c-SRC. Finally, HER2 and CB2 form heteromers in cancer cells. Our findings reveal an unprecedented role of CB2 as a pivotal regulator of HER2 pro-oncogenic signaling in breast cancer, and suggest that CB2 may be a biomarker with prognostic value in these tumors

Time-of-arrival in quantum mechanics

We study the problem of computing the probability for the time-of-arrival of a quantum particle at a given spatial position. We consider a solution to this problem based on the spectral decomposition of the particle's (Heisenberg) state into the eigenstates of a suitable operator, which we denote as the ``time-of-arrival'' operator. We discuss the general properties of this operator. We construct the operator explicitly in the simple case of a free nonrelativistic particle, and compare the probabilities it yields with the ones estimated indirectly in terms of the flux of the Schr\"odinger current. We derive a well defined uncertainty relation between time-of-arrival and energy; this result shows that the well known arguments against the existence of such a relation can be circumvented. Finally, we define a ``time-representation'' of the quantum mechanics of a free particle, in which the time-of-arrival is diagonal. Our results suggest that, contrary to what is commonly assumed, quantum mechanics exhibits a hidden equivalence between independent (time) and dependent (position) variables, analogous to the one revealed by the parametrized formalism in classical mechanics.Comment: Latex/Revtex, 20 pages. 2 figs included using epsf. Submitted to Phys. Rev.

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer.

Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM -/- patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors